Test Code PTHRP
Parathyroid Hormone-Related Peptide (PTHrP), Plasma

Reporting Name

Useful For

Diagnostic workup of patients with suspected hypercalcemia of
malignancy

Diagnostic workup of patients with hypercalcemia of unknown
origin

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Plasma EDTA

Specimen Required

Patient Preparation: Fasting

Collection Container/Tube: Ice-cooled, lavender top
(EDTA)

Submission
Container/Tube: Plastic vial

Specimen Volume: 0.7 mL

Collection Instructions: Spin specimen down in a
refrigerated centrifuge or in chilled centrifuge cups.

Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type

Temperature

Time

Plasma EDTA

Frozen

90 days

Reference Values

<2.0 pmol/L

Day(s) and Time(s) Performed

Monday through Thursday; 2 p.m.

Test Classification

This test was developed and its performance characteristics
determined by Mayo Clinic in a manner consistent with CLIA
requirements. This test has not been cleared or approved by the
U.S. Food and Drug Administration.

CPT Code Information

82397

LOINC Code Information

Test ID

Test Order Name

Order LOINC Value

PTHRP

PTH-Related Peptide

15087-0

Result ID

Test Result Name

Result LOINC Value

81774

PTH-Related Peptide

15087-0

Clinical Information

Hypercalcemia of malignancy is a common cause of hypercalcemia
in hospitalized patients. Hypercalcemia of malignancy is typically
not due to excess parathyroid hormone (PTH). In these disorders,
PTH is usually suppressed due to elevated serum calcium
concentrations. A variety of other mechanisms lead to inappropriate
hypercalcemia in hypercalcemia of malignancy. These include:

-Impaired renal function due to a tumor or its treatment

-Osteolytic activity within bony metastases

-Release of calcemic cytokines by non-osteolytic bony
metastases

-Ectopic 1-alpha hydroxylase activity in tumor tissues

-Secretion of humoral factors mimicking PTH action (humoral hypercalcemia of malignancy: HHM), usually
associated with secretion of parathyroid hormone-related peptide
(PTHrP) by the primary tumor (or more commonly its metastases)

-Other as yet unknown factors

Frequently, a single cause cannot be pinpointed. Amongst the
defined causes of the condition, PTHrP secretion is believed to be
the most common culprit.

PTHrP is a single monomeric peptide that exists in several
isoforms, ranging from approximately 60 amino acids to 173 amino
acids in size, which are created by differential splicing and
posttranslational processing by prohormone convertases. PTHrP is
produced in low concentrations by virtually all tissues. The
physiological role of PTHrP remains incompletely understood. Its
functions can be broadly divided into 5 categories, not all of
which are present in all PTHrP isoforms or in all tissues:

-Transepithelial calcium transport, particularly in the kidney
and mammary gland

-As an indispensable component of successful pregnancy and fetal
development (embryonic gene deletion is lethal in mammals)

PTHrP's diverse functions are mediated through a range of
different receptors, which are activated by different portions of
PTHrP. Among the many receptors that respond to PTHrP is the PTH
receptor, courtesy of the fact that 8 of the 13 N-terminal amino
acids of PTH and of 3 common PTHrP isoforms are identical. Since
most of PTHrP's actions in normal physiology are autocrine or
paracrine, with circulating levels being very low, this receptor
cross-talk only becomes relevant when there is extreme and
sustained overproduction of PTHrP. This is seen occasionally in
pregnancy, lactation and, rarely, in a variety of nonmalignant
diseases. However, it is most commonly observed when tumors secrete
PTHrP ectopically. In rough correlation with physiological
production levels of PTHrP in the corresponding healthy tissues,
ectopic PTHrP production is most commonly seen in carcinomas of
breast, lung (squamous), head and neck (squamous), kidney, bladder,
cervix, uterus, and ovary. Neuroendocrine tumors may also
occasionally produce PTHrP. Most other carcinomas, sarcomas, and
hematolymphatic malignancies only sporadically produce PTHrP, with
the notable exceptions of T-cell lymphomas and myeloma.

Interpretation

Depending on the patient population, up to 80% of patients with
malignant tumors and hypercalcemia will be suffering from humoral
hypercalcemia of malignancy (HHM). Of these, 50% to 70% might have
an elevated parathyroid hormone-related peptide (PTHrP) level.
These patients will also usually show typical biochemical changes
of excess parathyroid hormone (PTH)-receptor activation, namely,
besides the hypercalcemia, they might have hypophosphatemia,
hypercalcuria, hyperphosphaturia, and elevated serum alkaline
phosphatase. Their PTH levels will typically be less than 30 pg/mL
or undetectable.

In patients with biochemical findings that suggest, but do not
prove, primary hyperparathyroidism (eg, hypercalcemia, but normal
or near-normal serum phosphate, and a PTH level that is within the
population reference range but above 30 pg/mL), humoral
hypercalcemia of malignancy (HHM)should be considered as a
diagnostic possibility, particularly if the patient is elderly,
has a history of malignancy,, or risk factors for malignancy.
An elevated PTHrP level in such a patient is highly suggestive of
HHM as the cause for the hypercalcemia.